Chlorinated hydrocarbons constitute the largest class of toxic chemicals in EPA Superfund sites. One intriguing method of converting chlorinated hydrocarbons into less toxic chemicals is bioremediation, in which living organisms use or isolate the toxic chemicals as part of their biological function. Our broad, long-term objective is to use computational methods to guide the engineering of more efficient enzymes responsible for bioremediation. We will study first computational methods for describing reactions in model systems, then explore the use of these methods to describe reactions occurring in the active site of enzymes. We will focus on the conversion of 1,2-dichloroethane to 2-chloroethanol catalyzed the haloalkane dehalogenase. The mechanism and intermediate structures of this reaction are known. We will use two model systems: the reaction of chloride ion with methyl chloride in water, and the reaction of hydroxide ion with 1,2-dichloroethane in carbon tetrachloride. Ab initio quantum mechanical energies will be calculated and use to parameterize a potential energy function. Potentials of mean force will be calculated by Monte Carlo methods. The results from the model systems will be used to explore the reaction of dichloroethane in the active site of dehalogenase. The geometry of the active site at various points along the reaction pathway will be optimized using ab initio methods. The optimized structures will then be put back into the enzyme, and the reaction profile for the entire enzyme- substrate complex calculated with a free energy perturbation method.